The overall objective of the proposed Child Research Center at the Mount Sinai School of Medicine is to provide selected Young Pediatric Investigators an intellectual environment and core laboratory facilities to develop basic science research programs with a molecular genetics theme that will facilitate their career development as independent physician- investigators. Under the direction of the Principal Investigator and Program Director, a group of Established Investigators from the Departments of Pediatrics, Biochemistry, Biomathematics, Cell Biology and Anatomy, Molecular Biology and Neurobiology will provide basic science research opportunities for the Young Pediatric Investigator which have relevance to pediatric medicine and provide model systems for future independent research projects. Among these are research opportunities in: 1) molecular genetics of lysosomal storage diseases, 2) tissue-specific gene regulation of globin and heme as well as studies of the inherited porphyrias, 3) molecular studies of peroxisomal assembly and peroxisomal disorders, 4) molecular approaches to the development of new vaccines, 5) molecular studies of development by insertional mutagenesis in transgenic mice, 6) use of homologous recombination to generate murine models of human inherited disorders and developmental defects, 7) linkage and reverse- genetic studies to identify the gene for juvenile myoclonic epilepsy, 8) studies of hormonally-responsive gene expression, 9) molecular genetics of collagens in growth and development, 10) molecular studies of autoimmunity, and 11) development of gene therapy in animal model systems. A shared core laboratory will provide oligonucleotide synthesis, PCR, gene mapping and tissue culture services to facilitate young investigator research; the core laboratory will be cost effective and the Co-Directors will provide expertise for these and other molecular and cell biologic techniques. High-quality, newly-trained pediatricians will be recruited for this program from local and national pools and the Advisory Committee will make awards to the Center Pediatric Scientist and/or the Junior Pediatric Investigators. The Young Pediatric Investigators and the Established Investigators will participate in a weekly "Molecular Genetics" Journal Club and in biweekly research presentations. This center of excellence will provide the intellectual environment and core laboratory facilities to enhance the development of pediatric investigators who will become independent and apply their expertise in molecular genetics to current and future problems in pediatric medicine. Moreover, support of this program will enhance the development of research activities in the Department of Pediatrics and will provide important scientific and intellectual resources for the continued development of basic and clinical science in the Mount Sinai School of Medicine.